Papain-catalysed mechanochemical synthesis of oligopeptides by milling and twin-screw extrusion: application in the Juliá–Colonna enantioselective epoxidation

Abstract

Chemoenzymatic oligomerisation of l-amino acids was successfully developed using mechanochemical techniques.

Mechanoenzymatic Transformations in the Absence of Bulk Water: A More Natural Way of Using Enzymes

“…Hernández and co‐workers next applied the papain‐catalyzed mechanoenzymatic process to the preparation of oligopeptides . Oligomerization of the esters of either l ‐alanine, l ‐phenylalanine, l ‐leucine or glycine, in the presence of papain, afforded homopolypeptides with the degree of polymerization conveniently controlled by adjusting the duration of milling and the amount of water (Scheme ).…”

“… Mechanoenzymatic synthesis of oligopeptides from l ‐phenylalanine, l ‐leucine, l ‐alanine, and glycine methyl esters . A) Overall reaction scheme.…”

“…(B) and (C) are reproduced from ref. with permission. Copyright: 2018, The Royal Society of Chemistry.…”

“…Hernµndez and co-workers next applied the papain-catalyzed mechanoenzymatic process to the preparation of oligopeptides. [119] Oligomerization of the esters of either l-alanine, lphenylalanine, l-leucine or glycine, in the presenceo fp apain, afforded homopolypeptides with the degree of polymerization conveniently controlled by adjusting the duration of milling and the amount of water (Scheme 7). The yields with hydrophobic l-Phe and l-Leue sters were enhanced witha dditional water,w hereas anhydrous conditions were necessary to obtain good yields with the more hydrophilic l-Ala and Glye sters (Scheme 7B).…”

N‐Heterocyclic Carbene Acyl Anion Organocatalysis by Ball‐Milling

“…This process has been exemplified throughapplications to intermolecular-benzoin, intramolecular-benzoin, intermolecular-Stetter andi ntramolecular-Stetter reactions including asymmetric examples and demonstrates that this mode of mechanistically complex organocatalytic reactionc an operate under solvent-minimised conditions. [3] In several instances there have emerged trends and conceptual frameworks, and in others there is simply at ranslation to as olvent-minimised process. [1] Chemical reactions brought about by ball-milling constitute an area of mechanochemistry.T hat ar eactiont akes place under ball-milling conditions does, however, not necessarily meant hat the process is mechanicallyd riven.I ndeed, ballmilling reactions also typically feature solvent-free or solventminimised, high-concentrationa nd occasionally high-instantaneous/bulk-temperature conditions.…”